Modulation of integrin function in hematopoietic progenitor cells by CD43 engagement:: Possible involvement of protein tyrosine kinase and phospholipase C-γ
Modulation of integrin function in hematopoietic progenitor cells by CD43 engagement:: Possible involvement of protein tyrosine kinase and phospholipase C-γ
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DOI：
10.1182/blood.v93.10.3317.410k12_3317_3326
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发表时间：
1999-05-15
期刊：
影响因子：
20.3
通讯作者：
Broxmeyer, HE
中科院分区：
文献类型：
--
作者：
Anzai, N;Gotoh, A;Broxmeyer, HE
细胞与细胞外基质成分的附着对造血的调节至关重要。CD43是一种黏蛋白样跨膜唾液酸糖蛋白，表达于几乎所有的造血细胞表面。带有负电荷的胞外粘蛋白高度伸展的结构可能对造血细胞起到排斥屏障的作用，然而，一些研究人员已经证明CD43具有前黏附特性，并且CD43的结合被报道上调整合素介导的T细胞黏附。我们发现CD43与单抗(MoAbs)交联会增强整合素α4β1(VLA-4)和α5β1(VLA-5)依赖的人脐血CD34(+)细胞对纤维连接蛋白的黏附，CD34(+)CD38(Hi)，但不是CD34(+)CD38(-/low)细胞对刺激有显著的反应，这表明承诺的，而不是干细胞和更多的未成熟的祖细胞对CD43介导的整合素的激活敏感，为了阐明导致整合素激活的分子机制，我们使用了生长因子依赖的细胞系MO7E，CD43的交联会诱导MO7e细胞内几种分子的酪氨酸磷酸化，包括蛋白酪氨酸激酶Syk、原癌基因产物Cb1和磷脂酶C(PLC)-γ2。此外，蛋白酪氨酸激酶抑制剂赫比霉素A和PLC抑制剂U73122均可阻断CD43诱导的纤维连接蛋白黏附增强。这些结果表明，CD43介导的信号可能通过依赖蛋白酪氨酸激酶和PLC-γ激活的途径增加造血祖细胞对纤维连接蛋白的整合素亲和力。(C)1999年由美国血液病学会主办。
Attachment of cells to extracellular matrix components is critical for the regulation of hematopoiesis. CD43 is a mucin-like transmembrane sialoglycoprotein expressed on the surface of almost all hematopoietic cells. A highly extended structure of extracellular mucin with negative charge may function as a repulsive barrier to hematopoietic cells, However, some investigators have shown that CD43 has proadhesive properties, and engagement of CD43 has been reported to upregulate integrin-mediated cell adhesion in T cells. We found that cross-linking of CD43 with monoclonal antibodies (MoAbs) enhanced integrin alpha 4 beta 1 (very late antigen [VLA]-4) and alpha 5 beta 1 (VLA-5)-dependent adhesion of human cord blood CD34(+) cells to fibronectin, CD34(+) CD38(hi), but not CD34(+)CD38(-/low) cells responded significantly to the stimulus, suggesting that committed, but not stem and more immature progenitors are sensitive to CD43-mediated activation of integrin, To elucidate the molecular mechanism leading to integrin activation, we used the growth factor-dependent cell line MO7e, Cross-linking of CD43 induced tyrosine phosphorylation of several intracellular molecules including the protein tyrosine kinase Syk, the protooncogene product Cbl, and phospholipase C (PLC)-gamma 2 in MO7e cells. Moreover, protein tyrosine kinase inhibitor herbimycin A and PLC inhibitor U73122 both blocked CD43-induced enhancement of adhesion to fibronectin. These results indicate that signals mediated through CD43 may increase integrin affinity to fibronectin via a pathway dependent on protein tyrosine kinase and PLC-gamma activation in hematopoietic progenitors. (C) 1999 by The American Society of Hematology.